PROJECT SUMMARY Recent dramatic increases in the incidence of mosquito-borne diseases, like Malaria, Zika, Chikungunya and Dengue Fever, and the wide-spread resistance of mosquitoes to insecticides emphasizes the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on continued basic research on the biology of mosquitoes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression in organisms as diverse as plants, animals, insects and viruses. Sequence specific binding of miRNAs to complementary regions on mRNAs can either down-regulate or up- regulate expression of the encoded protein. A growing body of evidence indicates that miRNAs contribute to the control of tissue- and stage-specific gene expression in mosquitoes; playing key roles modulating sugar absorption, fluid excretion, blood intake and digestion, egg maturation and survival in Ae. aegypti. On the other hand, little is known about the role of miRNAs on the regulation of juvenile hormone (JH) biosynthesis in insects. In the female mosquito, JH signals the completion of the ecdysis to the adult stage, and initiates reproductive processes. JH titer is essentially determined by the rate at which the corpora allata (CA) synthesizes JH. High- throughput small RNA sequencing of CA showed dramatic alterations of miRNA profiles among the CA of pupa (low JH synthesis), sugar-fed (high JH synthesis) and blood fed (low JH synthesis) adult females. We now intend to further study the role of CA-specific and differentially expressed miRNAs in the regulation of JH biogenesis. Completing the proposed research could lead to the identification of targets for designing new, specific and affordable strategies suitable for mosquito control.